The following is a brief description of the synthesis of a lipid compound. This summary is not meant to be complete but is provided only for understanding of the invention that follows. This summary is not an admission that any of the work described below is prior art to the claimed invention.
N,N-Dioleyl-N,N-Dimethylammonium Chloride (DODAC) is an amphipathic compound which has been used for a variety of purposes. Several laboratories have reported the use of DODAC for the transfection of nucleic acid molecules into cells and mammalian organs, either independently or mixed with another compound (Ansell et al., International PCT Publication No. WO 96/10390; Wheeler et al, International PCT Publication No. WO 96/04964; Wasan et al, 1996, Can. J. Pharm. Sci. 85, 427-33; Reimer et al., 1995, Biochemistry 34, 12877-83).
DODAC has also been described as a component of certain liquid detergents (Inoe et al., Japanese Patent Application No. JP 08048995); and Inoe et al., Japanese Patent Application No. JP 94-184925), for use in hair treatment (Kaji et al., Japanese Patent Application No. JP 07330552; Yamamoto et al., Japanese Patent Application No. JP 07330551; and Ikeda et al., Japanese Patent Application No. JP 93-235708) and as a fabric softener (Umezawa et al., Japanese Patent Application No. JP 93-168582; Ide et al., Japanese Patent Application No. JP 05059670; Kobauashi et al., Japanese Patent Application No. JP 04222280; Takeuchi et al., Japanese Patent Application No. JP 04108172; and Inokoshi, Japanese Patent Application No. JP 02300381).
Ansell et al., supra describes two methods for the synthesis of DODAC. The first process involves the synthesis of DODAC through the formation of two intermediates for a total of three steps: 1) formation of N-oleyloleoylamide from oleylamine and oleic acid; 2) reduction of N-oleyloleoylamide to dioleylamine; and 3) methylation of dioleylamine to form DODAC.
The second method described in Ansell et al., is a two step approach which uses flammable dimethylamine gas in the first step. The quaternization reaction of this reaction scheme is conducted in the heterogeneous mixture of chloroform and aqueous NaOH at reflux temperature for 16 hours followed by treatment in concentrated hydrochloric acid and repeated extraction through chloroform.